Abdominal aortic aneurysm (AAA) is a focal enlargement of the infrarenal aorta. If left untreated, AAA will gradually expand until rupture, an event that carries a mortality rate of 90%. 15,000 Americans die each year from AAA rupture, making it the 13th most common cause of death in the US. Associated with repair of AAA are significant costs and risks to the patient. Thus, it is important to determine when the risk of rupture justifies the risks associated with surgery. The ability to reliably evaluate the susceptibility of a particular AAA to rupture could vastly improve the clinical management of these patients, as there presently exists no such reliable evaluation criterion. AAA rupture occurs when the mechanical stress acting on the aneurysm wall locally exceeds its failure strength. The greater the wall stress-to-wall strength ratio for a particular AAA, the greater the likelihood of rupture. We therefore believe that careful consideration of the Rupture Potential Index (RPI) would lead to an improved assessment of the propensity for rupture of AAA on a patient-specific basis. The RPI is defined as the locally acting wall stress divided by the local wall strength. As the RPI increases, so too does the possibility of AAA rupture. Our original grant, for which the current proposal serves as a competing renewal application, allowed us to develop methods to noninvasively determine the RPI distribution for AAA on a patient-specific basis. The working hypothesis of this proposal is that the RPI - i.e., the peak ratio of local wall stress to local wall strength - is a better predictor of AAA rupture than either the maximum aneurysm diameter or peak wall stress alone. To address this hypothesis, we will execute the following three specific aims: 1) Perform an "in-vitro validation" of our RPI technique using physical (i.e., custom-fabricated polymer) models of patient-specific AAA; 2) Perform a "retrospective clinical validation" of our RPI technique by analyzing existing data from patients who underwent AAA rupture (or were symptomatic prior to repair) and comparing to that from patients who's AAA did not rupture; and 3) Perform a "prospective clinical validation" of our RPI technique by collecting and analyzing data from patients with AAA followed over time in order to evaluate the time-course of RPI and its correlation with unfavorable clinical outcome. Successful validation of this novel, innovative, computationally-based, noninvasive method would allow an important paradigm shift to occur in AAA patient management and care by defining a new, more reliable criterion on which decisions to repair AAA will be based. This would greatly improve the clinical management for those afflicted with this disease. [unreadable] [unreadable] [unreadable]